An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab

Official Title: “An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab”

This open-label, rater-blinded extension study will enroll patients who have relapsing-remitting multiple sclerosis (RRMS) and who participated in one of three prior Genzyme-sponsored studies of alemtuzumab [CAMMS223 (NCT00050778), CAMMS323 (NCT00530348) also known as CARE-MS I, or CAMMS324 (NCT00548405) also known as CARE-MS II]. The purposes of this study are:

1. To examine the long term safety and efficacy of alemtuzumab treatment in patients who received alemtuzumab as their study treatment in one of the prior studies.

2. To examine the safety and efficacy of initial alemtuzumab treatment in this study for patients who received Rebif® (interferon beta-1a) as their study treatment in one of the prior studies.

3. To determine if and when further alemtuzumab treatment is needed, and the safety and efficacy of this "as needed" treatment. This applies both to patients who received alemtuzumab for the first time in one of the prior studies or for the first time in this extension study.

Alemtuzumab treatment will either be on a fixed schedule of two treatment cycles a year apart for patients who received Rebif® in one of the prior Genzyme-sponsored studies of alemtuzumab or on an as needed schedule (e.g. due to documented evidence of resumed MS activity) for patients who have already completed a fixed schedule of treatment with alemtuzumab in one of the prior Genzyme-sponsored studies. There is no comparison treatment in this study. All patients will be required to return to their study site every 3 months for neurologic and other assessments. In addition, safety-related laboratory tests and surveys will be performed at least monthly. Participation in the extension study will last 36 months from enrollment, but some patients may need additional safety follow-up via a separate mechanism beyond the 36 months.

Intervention(s) in this Clinical Trial

• Biological: alemtuzumab
  • 12 mg per day administered through IV, once a day for 3 consecutive days (patients may receive additional cycles of alemtuzumab upon documented evidence of resumed disease activity, but not within same 12-month period)
• Biological: alemtuzumab
  • 12 mg per day administered through IV, once a day for 5 consecutive days during the first cycle and 12 mg per day administered through IV, once a day for 3 consecutive days during the second cycle, 12 months later. Patients may qualify for as-needed retreatment (12 mg per day administered through IV, once a day for 3 consecutive days) after their second fixed annual cycle.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Previously treated with alemtuzumab
  • Patients treated with alemtuzumab in prior Genzyme-sponsored studies of alemtuzumab who show documented evidence of resumed disease activity
• Experimental: Previously treated with interferon beta-1a (Rebif®)
  • Patients treated with interferon beta-1a (Rebif®) in prior Genzyme-sponsored studies of alemtuzumab who meet treatment eligibility criteria.

Primary Measures

• Time to Sustained Accumulation of Disability (SAD)
  • Time Frame: Prior study baseline through Extension Month 36
    Safety Issue?: No
• Relapse Rate
  • Time Frame: Prior study baseline through Extension Month 36
    Safety Issue?: No

Secondary Measures

• Time to sustained reduction in disability (SRD) as measured by the EDSS (Expanded Disability Status Scale)
  • Time Frame: Prior study baseline through Extension Month 36
    Safety Issue?: No
• Change over time in EDSS scores
  • Time Frame: Prior study baseline through Extension Month 36
    Safety Issue?: No
• Change over time in MRI findings
  • Time Frame: Prior study baseline through Extension Month 36
    Safety Issue?: No
• Change over time in self-reported quality of life as assessed by the Medical Outcome Study SF-36 Version 2, FAMS (Functional Assessment of Multiple Sclerosis), and EQ-5D findings
  • Time Frame: Prior study baseline through Extension Month 36
    Safety Issue?: No

Inclusion Criteria:

• 1.Received alemtuzumab in CAMMS323 or CAMMS324, completed the 2-year study period, and have not subsequently received disease modifying treatments (other than glatiramer acetate or interferon beta); or
• 2.Received Rebif® in CAMMS323 or CAMMS324, completed the 2-year study period, and have not subsequently received alternative disease modifying treatments (other than glatiramer acetate or another interferon beta); or
• 3.Participated in CAMMS223.
• NOTE: Criteria 1 and 2 above mean that patients who enrolled in CAMMS323 or CAMMS324 but did not complete the 2-year study period or went on to receive non-study drug
• DMTs after randomization are not eligible for inclusion in the Extension Study.
• Patients who enrolled in CAMMS324 after participation in CAMMS223 must meet criteria 1 or 2 to be eligible for inclusion in the Extension Study.

Exclusion Criteria:

• Any alemtuzumab patient from CAMMS223, CAMMS323, or CAMMS324 who has received alemtuzumab off-label (ie, outside of one of the prior Genzyme-sponsored studies), or is participating in any other investigational study, unless approved by Genzyme. In addition, these patients must be screened for disqualifying safety concerns before receiving alemtuzumab retreatment.
• Any Rebif® patient from CAMMS223, CAMMS323, or CAMMS324 who meets any of the following criteria. In addition, these patients must be screened for disqualifying safety concerns before receiving alemtuzumab treatment. a)Does not wish to receive alemtuzumab; b) Ongoing participation in any other investigational study, unless approved by Genzyme; c)Has received alemtuzumab off-label (ie, outside of one of the prior Genzyme-sponsored studies); d)Known bleeding disorder or therapeutic anticoagulation; e)Diagnosis of idiopathic thrombocytopenia purpura or other autoimmune hematologic abnormality; f)History of malignancy, except basal cell skin carcinoma; g)Intolerance of pulsed corticosteroids, especially a history of steroid psychosis h)Significant Autoimmune disorder (other than MS); i)Major psychiatric disorder or epileptic seizures not adequately controlled by treatment; j)Active infection or high risk for infection k)Unwilling to use a reliable and acceptable contraceptive method during and for at least 6 months following each alemtuzumab treatment cycle (fertile patients only).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Genzyme Industry

Overall Clinical Trial Officials and Contacts

Medical Monitor Study Director Genzyme Coorporation  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00930553

Study ID Number: CAMMS03409

ClinicalTrials.gov Identifier: NCT00930553

Health Authority: United States: Food and Drug Administration